白藜芦醇通过核因子-κB信号通路抑制脑缺血基质金属蛋白酶功能上调

Effect of resveratrol on NF-κB-induced upregulation of MMP-9 function following cerebral ischemia

目的揭示白藜芦醇抑制脑缺血基质金属蛋白酶(MMP)-9功能上调的分子机制及其与核因子(NF)-κB信号通路联系。方法建立大鼠四动脉前脑缺血模型,采用免疫印迹技术观察缺血后再灌海马脑区MMP-9蛋白水平和NF-κB核易位的变化;给予自由基清除剂白藜芦醇或NF-κB抑制剂吡咯二硫氨基甲酸酯(PDTC),识别NF-κB信号通路是否参与了白藜芦醇对脑缺血MMP-9蛋白表达的调控。结果脑缺血/再灌诱导海马脑区MMP-9蛋白水平和NF-κB核易位增加(P<0.05)。PDTC能一定程度的抑制缺血后MMP-9基因表达(P<0.05)。白藜芦醇能显著抑制脑缺血NF-κB核易位和MMP-9表达上调(P<0.05)。结论脑缺血再灌,诱导MMP-9依赖NF-κB通路的蛋白水平增加,白藜芦醇能通过抑制NF-κB通路下调MMP-9的功能,继而阻断MMP-9激活介导的胞外基质降解及海马脑区损伤。

Objective To explore the molecular mechanisms underlying inhibiting MMP-9 function increasing resulted from cerebral ischemia by resveratrol and its relations with NF-KB signaling pathway. Methods Four arterial forebrain ischemia model of rats were estab- lished and the changes of MMP-9 ~mtein and NF-KB nuclear transfer were observed by adopting immunoblot assay after ischemia reperfusion in hippocampus. Results After ischemia reperfusion was adopted, MMP-9 protein level in hippocampus and NF-KB nuclear transfer were induced to increase. PDTC inhibited the increasing of MMP-9 expression to a certain degree after ischemia reperfusion~ Resveratrol signifi- cantly inhibited NF-KB nuclear transfer and MMP-9 expression after ischemia reperfusion. Conclusions MMP-9 expression depends on NF- KB pathway is increased as induced by reperfusion after cerebral ischemia. Resveratrol can inhibit the function of MMP-9 through NF-KB pathway, therefore blocking the extracellular matrix degradation and the damage to the hippocampus area which is resulted from the activation of MMP-9.